FOXO3A Regulates Peroxiredoxin III Expression in Human Cardiac Fibroblasts

We found that depletion of FOXO3A leads to a dramatic reduction of Prx III mRNA and protein in serum-deprived human cardiac fibroblasts

Calin B. Chiribau; Lihong Cheng; Ioan C. Cucoranu; Yong-Shen Yu; Roza E. Clempus; Dan Sorescu


Scholarcy highlights

  • Peroxiredoxins2 are antioxidant enzymes that modulate the cellular response to oxidative stress, in particular to
  • We identified two putative FOXO3A DNA binding sites in Prx III promoter at ؊267 and ؊244 nucleotides relative to the start codon. We demonstrated that both sequences are required for binding of endogenous FOXO3A to the Prx III promoter by performing electromobility shift assays and chromatin immunoprecipitation assays
  • Peroxiredoxins inactivate H2O2 by oxidizing a key cysteine residue in their catalytic center, which is subsequently reduced by thioredoxins, reduced by electrons from NADPH provided by cellular thioredoxin reductases
  • To test whether FOXO3A is necessary for the expression of Prx III, we depleted FOXO3A by transfecting human cardiac fibroblasts with specific small interference RNA
  • FOXO3A is important for reg- These results demonstrate that FOXO3A binds its cognate ulation of Prx III mRNA and protein in serum-deprived HCFb. sequences within the Prx III promoter in vitro
  • We provide evidence that FOXO3A is essential for expression of Prx III in response to serum deprivation in human cardiac fibroblasts
  • Prx III upregulation by FOXO3A is important for the survival response and protects against oxidative stress caused by serum deprivation

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